Drug Partitioning in Micellar Media and Its Implications in Rational Drug Design: Insights with Streptomycin

Abstract

Oral bioavailability of a drug molecule requires its effective delivery to the target site. In general, majority of synthetically developed molecular entities have high hydrophobic nature as well as low bioavailability, therefore the need for suitable delivery vehicles arises. Self-assembled structures such as micelles, niosomes, and liposomes have been used as effective delivery vehicles and studied extensively. However, the information available in literature is mostly qualitative in nature. We have quantitatively investigated the partitioning of antibiotic drug streptomycin into cationic, nonionic, and a mixture of cationic and nonionic surfactant micelles and its interaction with the transport protein serum albumin upon subsequent delivery. A combination of calorimetry and spectroscopy has been used to obtain the thermodynamic signatures associated with partitioning and interaction with the protein and the resulting conformational changes in the latter. The results have been correlated with other class of drugs of different nature to understand the role of molecular features in the partitioning process. These studies are oriented toward understanding the physical chemistry of partitioning of a variety of drug molecules into suitable delivery vehicles and hence establishing structure-property-energetics relationships. Such studies provide general guidelines toward a broader goal of rational drug design.

Correlating the Properties of Antibiotics with the Energetics of Partitioning in Colloidal Self-Assemblies and the Effect on the Binding of a Released Drug with a Target Protein

“…To ensure that the optimized concentrations of the surfactants retain their micellar form even in the presence of drugs, ITC was used to determine the critical micellar concentration (cmc). The values of cmc of TTAB and the enthalpy of micellization are 3.6 mM and 0.65 kJ mol –1 , respectively. , The ITC profiles shown in Figure S11 represent the demicellization process of 50 mM TTAB taken in a syringe upon titration into water or an aqueous drug solution taken in the cell of ITC. With an increase in the number of injections, the concentration of TTAB in the cell increases and micellization takes place.…”

“…We previously established that a combined calorimetric and spectroscopic approach can be used for a quantitative understanding of the partitioning of drugs in self-assemblies of surfactants. − However, to obtain meaningful correlations, a systematic variation in functionality on the drugs and surfactants on partitioning behavior needs to be investigated. In this work, we have chosen a broader class of antibiotics varying in hydrophobicity, functionality, surface polarity, steric factors, and orientation of the functional groups which can permit the establishment of structure–property–energetics correlations in the partitioning process.…”

<p>Recent Advances in Oral Nano-Antibiotics for Bacterial Infection Therapy</p>

“…107 Polymeric micelles play an important role in the oral delivery of antibiotics not only because of its good solubilization, high drug-loading, and controlled drug release, but also due to its ability to reduce the non-specific uptake by the reticuloendothelial system (RES) and to remain stable in the GIT. 28,108 Pyrinezolid, an oxazolidinone-based drug, is effective against many Gram-positive bacteria including methicillinresistant Staphylococcus aureus (MRSA) and vancomycinresistant Enterococcus albeit with poor solubility. Methoxy poly (ethylene glycol)-poly (lactide) (mPEG-PLLA) diblock copolymers were used to improve the oral bioavailability and lung targeting of pyrinezolid.…”

Streptomycin Sulfate–Loaded Niosomes Enables Increased Antimicrobial and Anti-Biofilm Activities

“…It cannot be taken orally and is often prescribed as regular intramuscular injections. Aminoglycosides block the protein synthesis in the bacterium by binding to the S12 protein of the 30 S ribosomal unit ( Judy et al, 2018 ); thus, they can have a bactericidal effect ( Zhu et al, 2001 ; Sharma et al, 2007 ; de Lima Procópio et al, 2012 ).…”